Intercellular recognition events are fundamental to many biological processes including fertilization, development, and the mounting of an immune response. Although little is known of the molecular mechanisms underlying cell recognition and adhesion, cell surface oligosaccharides have been implicated as key participants in many of these events. (Hughes, Curr. Opin. Struct. Biol. 2:687-92, 1992; Drickamer, et al., Annu. Rev. Cell Biol. 9:237-64, 1993; Bock, et al., "Carbohydrate Recognition in Cellular Function," John Wiley & Sons Ltd: Chichester, UK, 1989; Vol. 145.) Carbohydrate receptors often bind weakly to target saccharide ligands in solution (i.e., with K.sub.a' .dbd.10.sup.3 -10.sup.4 M). (Lee, Fed. Proc. Fed. Am. Soc. Exp. Biol. 6:3193-3200, 1992.) FIG. 1 describes the lectin concanavalin A (Con A) binding to multiple mannose residues on the surface of erythrocytes.
Thus, nature takes advantage of multivalent carbohydrate-protein interactions to enhance the strength of cell surface binding. (Karlsson, Annu. Rev. Biochem. 58:309-350, 1989; Goldhar, Methods Enzymol. 236:211-231, 1994.) Molecules that can mimic the polyvalent display of oligosaccharides presented by a cell surface should be more effective than monovalent ligands at modulating intercellular interactions (DeFrees, et al., J. Am. Chem. Soc. 115:7549-7550, 1993; Matrosovich, et al., FEBS Lett. 272:209-212, 1990; Spaltenstein, et al., J. Am. Chem. Soc. 113:686-687, 1991; Roy, et al., J. Chem. Soc., Chem. Commun. pp. 1869-1872, 1993; Kingery-Wood, et al., J. Am. Chem. Soc. 114:7303-5, 1992; Spevak, et al., J. Am. Chem. Soc. 115:1146-1147, 1993; Glick, et al., J. Biol. Chem. 266:23660-23669, 1991; Sabesan, et al., J. Am. Chem. Soc. 114:8363-75, 1992).
Three general approaches used for the synthesis of multivalent carbohydrate derivatives are (1) attachment of carbohydrate residues to an acrylamide polymer backbone (Matrosovich, et al., FEBS Lett. 272:209-212, 1990; Spaltenstein, et al., J. Am. Chem. Soc. 113:686-687, 1991; Roy, et al., J. Chem. Soc., Chem. Commun. pp. 1611-13, 1992), (2) incorporation of carbohydrate bearing lipids into liposomes (Kingery-Wood, et al., J. Am. Chem. Soc. 114:7303-5, 1992; Spevak, et al., J. Am. Chem. Soc. 115:1146-1147, 1993) and (3) conjugation of carbohydrate groups to a protein (Welply, et al., Glycobiology 4:259-265, 1994). With these methods, it is difficult to control the size of the multivalent ligand and the density of carbohydrate substituents.
We sought an alternative polymerization method that would have the potential for greater control of polymer size, structure, and the density of carbohydrate substituents. In addition, we wanted a flexible strategy that would allow the production of copolymers to synthesize materials for selective immobilization of different cell types. Finally, the chosen polymerization reaction should tolerate a highly polar monomer bearing unprotected sugars.